ClinicalTrials.gov
ClinicalTrials.gov Menu

A Study to Investigate Safety and Tolerability, Pharmacokinetics, Pharmacodynamics and Food Effect of JNJ-54175446 in Healthy Participants

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02475148
Recruitment Status : Completed
First Posted : June 18, 2015
Last Update Posted : February 7, 2017
Sponsor:
Information provided by (Responsible Party):
Janssen-Cilag International NV

Brief Summary:
The purpose of this study is to investigate the safety and tolerability of JNJ-54175446 versus placebo after single oral dose administration (ascending dose levels), to determine the maximal tolerated dose (MTD) or the safety and tolerability at exposures resulting in full target engagement for at least 24 hours in all participants (whichever comes first), to characterize the pharmacokinetics of JNJ-54175446 in plasma, cerebrospinal fluid (CSF) and urine and to investigate the effect of food (high fat/high calorie) on the pharmacokinetics of JNJ 54175446 after single oral dose administration.

Condition or disease Intervention/treatment Phase
Healthy Drug: JNJ 54175446 Drug: Placebo Other: High fat/high Calorie Breakfast Phase 1

Detailed Description:
This is a double-blind, placebo-controlled, randomized, single ascending dose study in healthy participants for JNJ-54175446. The study will consist of 3 phases: a screening phase (between 21 and 2 days prior to dose administration), a double-blind treatment phase (8 days; Part 1 and Part 3) or an open-label treatment phase (8 days; Part 2), and a follow-up examination (within 14 to 21 days after dose administration). The maximal study duration for a participant will not exceed 6 weeks. In each cohort of Part 1 (6 cohorts) and Part 3 (1 cohort), participants will be randomly assigned to receive JNJ-54175446 or matching placebo and in cohort of part 2, all participants will be assigned to JNJ-54175446 treatment. In part 1, primarily maximum tolerated dose (MTD) will be assessed, along with safety and tolerability of JNJ-54175446. In part 2, pharmacokinetics (PK) of JNJ-54175446 in cerebrospinal fluid (CSF) will be assessed. In part 3, the effect of food on the plasma PK of JNJ-54175446 in young healthy male participants will be assessed. Safety will be monitored throughout the study.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 76 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: A Randomized, Placebo-controlled, Double-blind, Single Ascending Dose Study to Investigate Safety and Tolerability, Pharmacokinetics, Pharmacodynamics and Food Effect of JNJ-54175446 in Healthy Subjects
Study Start Date : June 2015
Actual Primary Completion Date : October 2015
Actual Study Completion Date : October 2015

Arm Intervention/treatment
Experimental: Part 1: Cohort 1
Participants will receive either JNJ-54175446 0.5 milligram (mg) or placebo on Day 1.
Drug: JNJ 54175446
Drug: Placebo
Experimental: Part 1: Cohort 2
Participants will receive either JNJ-54175446 2.5 mg or placebo on Day 1.
Drug: JNJ 54175446
Drug: Placebo
Experimental: Part 1: Cohort 3
Participants will receive either JNJ-54175446 10 mg or placebo on Day 1.
Drug: JNJ 54175446
Drug: Placebo
Experimental: Part 1: Cohort 4
Participants will receive either JNJ-54175446 30 mg or placebo on Day 1.
Drug: JNJ 54175446
Drug: Placebo
Experimental: Part 1: Cohort 5
Participants will receive either JNJ-54175446 100 mg or placebo on Day 1.
Drug: JNJ 54175446
Drug: Placebo
Experimental: Part 1: Cohort 6
Participants will receive either JNJ-54175446 200 mg or placebo on Day 1.
Drug: JNJ 54175446
Drug: Placebo
Experimental: Part 2: Cohort 7
Participants will receive JNJ-54175446 on Day 1. The dose of JNJ-54175446 will be determined in part 1 as suitable dose.
Drug: JNJ 54175446
Experimental: Part 3: Cohort 8
Participants will receive JNJ-54175446 on Day 1 along with high fat/high calorie breakfast. The dose of JNJ-54175446 will be determined in part 1 as suitable dose.
Drug: JNJ 54175446
Drug: Placebo
Other: High fat/high Calorie Breakfast



Primary Outcome Measures :
  1. Number of Participants with Adverse Events [ Time Frame: Baseline up to 14 or 21 days after study drug administration ]
    An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.

  2. Maximum Tolerated Dose of JNJ-54175446 in Part 1 [ Time Frame: Baseline up to 24 Hours after study drug administration ]
  3. Maximum Observed Plasma and Cerebrospinal Fluid (CSF) Concentration (Cmax) [ Time Frame: Pre-dose; 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, 18, 24, 36, 48, 72, 96, 120, 144 hours after study drug administration ]
    The Cmax is the maximum observed concentration.

  4. Last Quantifiable Plasma and Cerebrospinal Fluid (CSF) Concentration (Clast) [ Time Frame: Pre-dose; 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, 18, 24, 36, 48, 72, 96, 120, 144 hours after study drug administration ]
  5. Time to Reach Maximum Observed Plasma and Cerebrospinal Fluid Concentration (Tmax) [ Time Frame: Pre-dose; 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, 18, 24, 36, 48, 72, 96, 120, 144 hours after study drug administration ]
  6. Time to Last Quantifiable Plasma and Cerebrospinal Fluid Concentration (Tlast) [ Time Frame: Pre-dose; 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, 18, 24, 36, 48, 72, 96, 120, 144 hours after study drug administration ]
  7. Area Under Curve From Time of Administration up to the Last Time Point with a Measurable Plasma and Cerebrospinal Fluid Concentration (AUClast) [ Time Frame: Pre-dose; 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, 18, 24, 36, 48, 72, 96, 120, 144 hours after study drug administration ]
  8. Area Under the Plasma and Cerebrospinal Fluid Concentration-Time Curve From Time Zero to Infinite Time (AUC[0-infinity]) [ Time Frame: Pre-dose; 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, 18, 24, 36, 48, 72, 96, 120, 144 hours after study drug administration ]
  9. First-order Rate Constant (Lambda[z]) [ Time Frame: Pre-dose; 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, 18, 24, 36, 48, 72, 96, 120, 144 hours after study drug administration ]
  10. Elimination Half-Life (t1/2) [ Time Frame: Pre-dose; 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, 18, 24, 36, 48, 72, 96, 120, 144 hours after study drug administration ]
    The elimination half-life (t1/2) is the time measured for the plasma/CSF concentration to decrease by 1 half to its original concentration. It is associated with the terminal slope of the semi logarithmic drug concentration-time curve, and is calculated as 0.693/lambda(z).

  11. Total Clearance (CL/F) [ Time Frame: Pre-dose; 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, 18, 24, 36, 48, 72, 96, 120, 144 hours after study drug administration ]
    Total clearance of drug after extravascular administration, uncorrected for absolute bioavailability

  12. Creatinine Clearance [ Time Frame: Pre-dose; 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, 18, 24, 36, 48, 72, 96, 120, 144 hours after study drug administration ]
    Creatinine clearance was calculated by Cockroft-Gault formula. Creatinine clearance is equal to 140 minus age multiplied by weight and constant (1 for men and 0.85 for women) divided by creatinine in (micro mole per liter).



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Participants must have a body mass index (BMI) between 18 and 32 kg/m^2, inclusive (BMI = weight/height^2)
  • Participants must be healthy on the basis of clinical laboratory tests performed at screening. If the results of the serum chemistry panel[excluding liver function tests], hematology, or urinalysis are outside the normal reference ranges, the participant may be included only if the investigator judges the abnormalities to be not clinically significant. This determination must be recorded in the subject's source documents and initialed by the investigator
  • A man who is sexually active with a woman of childbearing potential and has not had a vasectomy must agree to use a barrier method of birth control e.g., either condom with spermicidal foam/gel/film/cream/suppository or partner with occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository, and all men must also not donate sperm during the study and for 3 months after receiving the last dose of study drug. In addition, their female partner should also use an appropriate method of birth control for at least the same duration

For Part 1 and 3:

- Healthy male participants between 18 and 54 years of age, inclusive

For Part 2:

  • Healthy male or female participants between 55 and 75 years of age, inclusive
  • Participant must be healthy on the basis of both physical and neurological examination performed at screening and at admission to the clinical unit
  • Women must not be of childbearing potential (i.e., must be postmenopausal with amenorrhea for at least 12 months); permanently sterilized (e.g., tubal occlusion, hysterectomy, bilateral salpingectomy); or otherwise be incapable of pregnancy

Exclusion Criteria:

  • Participant has a history of or current liver or renal insufficiency; significant cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurologic, hematologic (including coagulation disorders), rheumatologic, psychiatric, or metabolic disturbances, any inflammatory illness or any other illness that the Investigator considers should exclude the participant
  • Participant has any liver function test (including alanine aminotransferase [ALT], aspartate aminotransferase [AST], gamma-glutamyltransferase [gamma-GT], alkaline phosphatase [ALP] and bilirubin) at screening exceeding the upper limit of normal
  • Participant has a history of hepatitis B surface antigen (HBsAg) or hepatitis C antibody (anti-HCV) positive, or other clinically active liver disease, or tests positive for HBsAg or anti-HCV at Screening
  • Participant has a history of human immunodeficiency virus (HIV) antibody positive, or tests positive for HIV at Screening
  • Participant has a Prothrombin time [PT] >14 seconds and/or an activated partial thromboplastin time [aPTT] >35 seconds

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02475148


Locations
Belgium
Merksem, Belgium
Sponsors and Collaborators
Janssen-Cilag International NV
Investigators
Study Director: Janssen-Cilag International NV Clinical Trial Janssen-Cilag International NV

Responsible Party: Janssen-Cilag International NV
ClinicalTrials.gov Identifier: NCT02475148     History of Changes
Other Study ID Numbers: CR107482
2015-000942-53 ( EudraCT Number )
54175446EDI1001 ( Other Identifier: Janssen-Cilag International NV )
First Posted: June 18, 2015    Key Record Dates
Last Update Posted: February 7, 2017
Last Verified: February 2017

Keywords provided by Janssen-Cilag International NV:
JNJ-54175446
Healthy